代谢综合征相关新因子的探讨
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摘要
目的:探讨新诊断代谢综合征患者脂联素水平的变化。
     实验设计:横断面、病例对照研究。
     方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫反应法测定血清脂联素水平,研究代谢综合征及其相关疾病脂联素水平的变化。
     结果:①男性脂联素水平低于女性[4.44(0.97-16.55)vs.7.591.29-23.29)ug/ml,P<0.001]。校正BMI水平后这种差别仍然存在(P<0.001)。不同年龄研究对象脂联素水平没有差别。②校正年龄和性别后,血清脂联素水平与HDL-C、ANGPTL3水平正相关(P<0.05),与BMI、WC、WHR、体脂含量、FPG、TG、UA、FINS、HOMA-IR、hsCRP水平负相关(P<0.05)。校正年龄、性别和BMI后,血清脂联素仍与HDL-C、ANGPTL3水平正相关(P<0.05),与FPG、TG、UA、FINS、HOMA-IR负相关(P<0.05),与WC、WHR、体脂含量和hsCRP水平负相关消失。TG、ANGPTL3、性别和HOMA-IR,是血清脂联素水平的独立决定因素。③无论男性还是女性,高血压患者血清脂联素水平与对照组比较,无明显差别[(4.77(1.01-23.29) vs.5.17(0.97-22.27)ug/ml,P=0.991)]。④肥胖组、超重组脂联素水平低于体重正常组[4.34(1.61-15.09)vs.4.28(0.97-22.27)vs.5.99(1.16-23.29)ug/ml,P=0.001],而超重组和肥胖组之间没有差别。⑤校正年龄和性别后,高TG组与对照组脂联素水平低于对照组[4.40(0.97-23.29)vs.6.67(1.12-22.27)ug/ml,P=0.001)]。校正年龄和性别后,低HDL-C组低于对照组脂联素水平[4.96(0.97-14.88)vs.5.18(1.12-23.29)ug/ml,P=0.005)]。⑥校正年龄和性别后,糖耐量异常和正常糖耐量组的脂联素水平高于2型糖尿病[5.05(1.06-23.29)vs.5.50(0.97-22,27 vs.3.13(1.01-13.57)ug/ml,P<0.001)],而糖耐量正常组和糖耐量异常组无明显差别。⑦校正年龄和性别后高尿酸血症组脂联素低于对照组[3.9(1.20-13.72)vs.5.4(0.97-23.29)ug/ml,P=0.004]。⑧校正性别和年龄后,NAFLD组脂联素水平低于对照组[4.18(1.01-15.09)vs.6.3(0.97-23.29)ug/ml,P<0.001]。校正年龄、性别和BMI后这种差别仍然存在(P=0.013)。⑨校正年龄和性别后代谢综合征组脂联素浓度低于对照组[4.22(1.01-23.29 vs.5.41(0.97-22.27)ug/ml,P=0.002]。不同代谢综合征定义下的代谢综合征组的脂联素水平均低于其对照组。不同代谢综合征定义的代谢综合征组的脂联素水平无差别(P=0.909)。随着代谢异常数目的增加,脂联素水平降低(P=0.001)。从2个组分开始脂联素水平就开始降低。但是2个组分以上脂联素水平的不再降低。代谢综合征合并糖耐量异常或2型糖尿病脂联素水平低于未合并血糖异常者。高浓度脂联素组代谢综合征患病率低于低浓度脂联素组(P<0.001)。
     结论:除了高血压,代谢综合征及其组分脂联素水平降低;高尿酸血症者脂联素水平降低。NAFLD脂联素水平降低。
     目的:探讨新诊断代谢综合征患者血管生成素样蛋白3(ANGPTL3)水平的变化。
     设计:横断面、病例对照研究
     方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫反应法测定血清ANGPTL3水平,研究代谢综合征及其相关疾病ANGPTL3水平的变化。
     结果:①男性和女性ANGPTL3水平没有差别(418.84±140.90 vs.437.22±160.46 ng/ml,P=0.384)。男性<50岁ANGPTL3水平低于>50岁者(p=0.009),校正BMI水平后这种差别仍然存在。女性不同年龄研究对象ANGPTL3水平没有差别。②校正年龄和性别后,血清ANGPTL3水平与脂联素水平正相关(P<0.001),与FINS、HOMAIR水平负相关(P=0.026和P=0.015)。校正年龄、性别和BMI后,血清ANGPTL3水平仍与脂联素水平正相关(P<0.001),与LDL-C水平正相关(P=0.049),但与FINS、HOMAIR水平负相关消失(P=0.118和P=0.0861。脂联素是血清ANGPTL3的独立决定因素。③校正年龄和性别后高血压患者血清ANGPTL3水平与对照组无差别(423.96±143.17 vs.421.24±153.72 ng/ml,P=0.894)。④校正年龄和性别后正常组、超重组、肥胖组三组间ANGPTL3水平有差异(453.51±145.28 vs.380.47±127.80 vs.450.73±161.37 ng/ml,P<0.001)。肥胖组、体重正常组高于超重组,但正常体重组和肥胖组之间没有差别;校正年龄、性别和脂联素后三组ANGPTL3水平仍有差别(F=5.572,P=0.004)。⑤校正年龄和性别后,高TG组与对照组ANGPTL3水平(424.69±154.06 vs.421.92±138.16 ng/ml,P=0.878)无差别。校正年龄和性别后,低HDL-C组与对照组ANGPTL3水平(428.46±134.06 vs.416.94±158.81 ng/ml,P=0.531)无差别。⑥2型糖尿病、糖耐量异常和正常糖耐量组ANGPTL3水平无差别。⑦高尿酸血症组与对照组ANGPTL3水平没有差别(428.48±144.52 vs.409.09±138.0ng/ml,P=0.374)。⑧NAFLD组ANGPTL3水平与对照组无差别(414.19±143.67 vs.435.41±144.58 ng/ml,P=0.256)。⑨代谢综合征组ANGPTL3水平与对照组相比,无差别(418.81±148.45 vs.426.49±144.10 ng/ml,P=0.674)。
     结论:血清ANGPTL3与脂联素水平独立正相关,而与TG和HDL-C无关,血清脂联素水平是ANGPTL3的独立决定因素。超重者ANGPTL3水平降低。
     目的:探讨新诊断代谢综合征患者血清视黄醇结合蛋白4水平的变化。
     方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫法反应测定血清视黄醇结合蛋白4(RBP4)水平,研究代谢综合征及其相关疾病RBP4水平的变化。
     结果:①男性RBP4水平高于女性(54.11±17.08 vs.38.72±12.46ug/ml,P<0.001);②校正年龄和性别后,血清RBP4水平与BMI、腰围、WHR、PBG,TG,CHOL、LDL、SBP、DBP、FINS、HOMA-IR、脂肪百分比和尿酸正相关(P<0.05),与HDL-C水平负相关(P=0.012);⑧TG、性别(男性=1,女性=2)、DBP、尿酸是血清RBP4的独立决定因素;④高四分位胰岛素抵抗者RBP4水平高于低四分位者(P=0.029);⑤男性高血压者RBP4水平高于无高血压者(61.96±19.16vs.51.28±15.38 ug/ml,P<0.001),女性高血压患者血清RBP4水平与对照组比较,无差别(P=0.551);校正年龄和性别后,超重组和肥胖组RBP4水平均高于体重正常组(45.75±16.11 vs.52.45±17.79 vs。55.60±16.94 ug/ml,P=0.026),但是超重组和肥胖组之间没有差别(P=0.274);校正年龄和性别后,高TG组RBP4水平高于对照组(55.22±17.72 vs.45.21±17.72 ug/ml,P<0.001);2型糖尿病组RBP4水平与糖耐量正常组、糖耐量异常组无差别(50.10±20.04 vs.48.38±14.67vs.53.96±19.23 ug/ml,P=0.074);⑥校正年龄和性别后高尿酸血症组RBP4浓度高于对照组(57.62±15.69 vs.48.43±16.88 ug/ml,P=0.032);⑦校正年龄和性别后,NAFLD组RBP4水平高于对照组(55.22±17.99 vs.47.44±15.24ug/ml,P=0.019);⑧校正年龄和性别后,代谢综合征组的RBP4水平高于对照组(54.79±18.32 vs.47.23±15.96ug/ml,P=0.002);随着代谢异常数目的增加,RBP4水平增加(P<0.001);高浓度RBP4组代谢综合征患病率高于低浓度组(P=0.002)。
     结论:RBP4与肥胖和代谢综合征相关,TG、性别、DBP和尿酸是血清RBP4的独立决定因素。高尿酸血症、非酒精性脂肪性肝病RBP4水平升高。
     目的:探讨新诊断代谢综合征患者血清中性粒细胞明胶酶相关脂笼蛋白2水平的变化。
     设计:横断面、病例对照研究
     方法:选取111例代谢综合征患者和152例无代谢综合征者作为对照组,收集人口学资料和测定生化指标,采用单克隆抗体双抗体夹心酶联免疫反应法测定血清中性粒细胞明胶酶相关脂笼蛋白(LCN2)水平,研究代谢综合征及其相关疾病LCN2水平的变化。
     结果:①男性和女性LCN2水平没有差别[30.37(9.25-123.25 vs.26.37(9.75-82.5)ug/L,P=0.541]。不同年龄研究对象LCN2水平没有差别。②校正年龄和性别后,血清LCN2水平与BMI、腰围、体脂含量、hsCRP正相关(P<0.05),与HDL-C水平负相关(P=0.001)。校正年龄、性别和BMI后,血清LCN2水平与hsCRP正相关(P<0.05),与HDL-C水平负相关(P=0.023)。但是与腰围、体脂含量的正相关消失。HDL-C和hsCRP是血清LCN2的独立相关因素。③高血压患者血清LCN2水平与对照组无差别[29.25(10.75-123.25) vs.28(9.25-92.25)ug/L,P=0.741]。④正常组、超重组和肥胖组三组间LCN2水平有差异[29.0(10.75-82.50) vs. 26.75(9.25-86.5) vs.36.37(13-123.25)ug/L,P=0.018]。肥胖组LCN2水平高于正常体重组和超重组,但正常体重组和超重组之间没有差别。校正hsCRP、HDL-C水平后三个不同BMI组别之间LCN2水平仍有差异(P=0.046)。⑤校正年龄和性别后,高TG组与对照组LCN2水平无差别[29.0(10.75-86.5)vs.29.0(9.25-123.25)ug/L;P=0.676]。校正年龄和性别后,低HDL-C组LCN2水平高于对照组[32.62(9.75-82.50) vs.26.37(9.25-123.25)ug/L,P=0.001];校正BMI、hsCRP后,这种差别仍然存在(F=8.27,P=0.004)。⑥糖耐量正常、糖耐量异常和2型糖尿病组LCN2水平有差异[32.5(9.75-89.5) vs.32.25(9.25-92.25) vs.27.0(10.75-123.25)ug/L,P=0.008],2型糖尿病组LCN2水平高于糖耐量正常组(P=0.024),糖耐量异常组高于糖耐量正常组(P=0.006),但是其水平在2型糖尿病组与糖耐量异常组无差别(P=0.945)。校正年龄和性别后三组比较F=4.29,P=0.015;校正年龄、性别、BMI后三组比较F=2.876,P=0.058。⑦高尿酸血症组与对照组LCN2水平无差别[29.12(9.25-130.25) vs.30(13-123.25)ug/L,P=0.247]。⑧NAFLD组LCN2水平与对照组无差别[32.37(9.25-130.25)vs.28.37(10.75-123.25)ug/L,P=0.134]。⑨校正年龄和性别后代谢综合征组LCN2水平高于对照组[32.37(9.25-156.5)vs.28(10.75-118.25)ug/L,P=0.032]。不同代谢综合征定义下的代谢综合征组的LCN2水平均高于其对照组。不同代谢综合征定义的代谢综合征组的LCN2水平无差别(P=0.987)。随着代谢异常数目的增加,LCN2水平增加没有达到统计学意义(校正年龄性别后, F=1.891,P=0.096)。随着LCN2浓度增加,代谢综合征患病率增加没有达到统计学意义(P=0.081)。
     结论:血清LCN2水平与hsCRP独立正相关,可以作为新的与肥胖和代谢综合征相关的炎症指标。低HDL-C血症者、2型糖尿病、糖耐量异常者、肥胖者与对照组比较,LCN2水平升高。代谢综合征患者LCN2水平升高。
Object: To evaluate serum adiponectin distribution and its association with metabolic syndrome.
     Design: Cross-sectional and case control study.
     Methods: 111 MetS cases and 152 controls were measured serum adiponectin levels with sandwich ELISA.
     Results:①Serum adiponectin levels in men were significantly lower than those in women [4.44(0.97-16.55) vs. 7.59(1.29-23.29) ug/ml, P<0.001].The difference did not disappear after adjusted for BMI (P<0.001). No age-associated difference in serum adiponectin levels was observed.②Serum adiponectin concentrations were positively correlated with HDL-C and ANGPTL3 (P<0.05) after adjusted for age and sex. Serum adiponectin concentrations were negatively correlated with BMI, WC, WHR, fat percentage, FPG,TG,UA, FINS, HOMAIR, and hsCRP (P<0.05). TG, ANGPTL3, sex, and HOMA-IR were found to be independent determinants for serum adiponectin concentrations.③No difference in serum adiponectin levels was observed between the hypertension and the control group [(4.77(1.01-23.29) vs. 5.17(0.97-22.27) ug/ml, P=0.991)].④Serum adiponectin concentrations were lower in the obesity and overweight groups than in the lean group [4.34(1.61-15.09) vs. 4.28(0.97-22.27) vs. 5.99(1.16-23.29) ug/ml , P=0.001]. No difference in serum adiponectin levels was observed between the overweight and the obesity group.⑤Serum adiponectin concentrations were significantly lower in the hypertriglyceridemia than in the control group [4.40(0.97-23.29) vs. 6.67(1.12-22.27) ug/ml, P=0.001)]. Serum adiponectin concentrations were significantly lower in the hypo-high density lipoproteinemia than in the control group [4.96(0.97-14.88) vs. 5.18(1.12-23.29) ug/ml, P=0.005)].⑥Serum adiponectin concentrations were significantly lower in the T2DM than in the NGT and IGT groups [5.05(1.06-23.29) vs. 5.50(0.97-22.27) vs. 3.13(1.01-13.57) ug/ml, P<0.001]. No difference in serum adiponectin levels was observed between the NGT and the IGT groups.⑦Serum adiponectin concentrations were significantly lower in the hyperuricemia than in the control group [3.9(1.20-13.72) vs. 5.4(0.97-23.29) ug/ml, P=0.004].⑧Serum adiponectin concentrations were significantly lower in the NAFLD than in the control group [4.18(1.01-15.09) vs. 6.3(0.97-23.29) ug/ml, P<0.001].⑨Serum adiponectin concentrations were significantly lower in the metabolic syndrome than in the control group [4.22(1.01-23.29) vs. 5.41(0.97-22.27) ug/ml, P=0.002]. Serum adiponectin concentrations were all significantly lower in the metabolic syndrome than in the control group under different metabolic syndrome definitions. There were no differences in adiponectin levels among metabolic syndrome groups by different definitions (P=0.909) . Serum adiponectin concentrations were significantly lower with more metabolic disorders. In the highest adiponectin tertile, the MetS risk was significantly lower than in the lowest tertile.
     Conclusion: Each component of metabolic syndrome, except for blood pressure, showed significantly lower serum adiponectin concentrations for both men and women. Serum circulating adiponectin concentrations are decreased in human subjects with hyperuricemia.
     Object: To evaluate serum angiopoietin -like protein 3 (ANGFTL3) distributions and its association with metabolic syndrome.
     Design: Cross-sectional and case control study.
     Methods: 111 MetS cases and 152 controls were measured serum ANGPTL3 levels with sandwich ELISA.
     Results:①No gender-associated difference in serum ANGPTL3 levels was observed(418.84±140.90 vs. 437.22±160.46 ng/ml, P=0.384). Serum ANGPTL3 levels in men > 50 years were significantly higher than those <50 years.②Serum ANGPTL3 concentrations were positively correlated with adiponectin (P<0.05) after adjusted for age and sex. Serum ANGPTL3 concentrations were negatively correlated with FINS and HOMA-IR (P<0.05). Adiponectin was found to be independent determinant for serum ANGPTL3 concentrations.③No difference in serum ANGPTL3 levels was observed between the hypertension and the control group (423.96±143.17 vs. 421.24±153.72 ng/ml, P=0.894).④Serum ANGPTL3 concentrations were lower in the overweight group than in the lean and obesity group (453.51±145.28 vs. 380.47±127.80 vs. 450.73±161.37ng/ml,P<0.001).⑤Serum ANGPTL3 concentrations were no significantly difference between hypertriglyceridemia and control group (424.69±154.06 vs. 421.92±138.16ng/ml, P=0.878). No difference in serum ANGPTL3 levels was observed between the hypo-high density lipoproteinemia and the control group (428.46±134.06 vs. 416.94±158.81 ng/ml, P=0.531).⑥No difference in serum ANGPTL3 levels was observed among NGT, IGT and T2DM groups.⑦No difference in serum ANGPTL3 levels was observed between the hyperuricemia and the control group (428.48±144.52 vs. 409.09±138.0ng/ml, P=0.374).⑧No difference in serum ANGPTL3 levels was observed between the NAFLD and the control group (414.19±143.67 vs. 435.41±144.58 ng/ml, P=0.256).⑨No difference in serum ANGPTL3 levels was observed between the metabolic syndrome and the control group (418.81±148.45 vs. 426.49±144.10 ng/ml, P=0.674).
     Conclusions: Serum ANGPTL3 concentrations were independently positively correlated with adiponectin, but not correlated with TG and HDL-C.
     Object: To evaluate serum Retinol-binding protein 4 (RBP4) distributions and its association with metabolic syndrome.
     Design: Cross-sectional and case control study.
     Methods: 111 MetS cases and 152 controls were measured serum RBP4 levels with sandwich ELISA.
     Results:①Serum RBP4 levels in men were significantly higher than those in women (54.11±17.08 vs. 38.72±12.46 ug/ml, P<0.001). No age-associated difference in serum RBP4 levels was observed.②Serum RBP4 concentrations were positively correlated with BMI, WC, WHR, PBG,TG,CHOL, LDL, SBP, DBP, FINS, HOMA-IR, fat percentage and UA(P<0.05)after adjusted for sex and age. Serum RBP4 concentrations were negatively correlated with HDL-C (P<0.05). TG,sex(male=1, female=2), DBP and UA were found to be independent determinants for serum RBP4 concentrations.③Serum RBP4 concentrations were higher in the hypertension in men than the control group [61.96±19.16 vs. 51.28±15.38ug/ml, P<0.001].④Serum RBP4 concentrations were higher in the obesity and overweight groups than in the lean group (45.75±16.11 vs. 52.45±17.79 vs. 55.60±16.94ug/ml, P=0.026). No difference in serum RBP4 levels was observed between the overweight and the obesity group (P=0.274).⑤No difference in serum RBP4 levels was observed among the NGT, IGT and T2DM groups (50.10±20.04 vs. 48.38±14.67 vs. 53.96±19.23ug/ml, P=0.074).⑥Serum RBP4 concentrations were significantly higher in the hypertriglyceridemia than in the control group (55.22±17.72 vs. 45.21±17.72ug/ml, P<0.001).⑦Serum RBP4 concentrations were significantly higher in the hyperuricemia than in the control group (57.62±15.69 vs.48.43±16.88, P=0.032).⑧Serum RBP4 concentrations were significantly higher in the NAFLD than in the control group (55.22±17.99 vs. 47.44±15.24ug/ml, P=0.019).⑨Serum RBP4 concentrations were significantly higher in the_metabolic syndrome than in the control group (54.79±18.32 vs. 47.23±15.96 ug/ml , P=0.002). Serum RBP4 concentrations were all significantly higher in the metabolic syndrome than in the control group under different metabolic syndrome definitions. There was no difference in RBP4 levels among metabolic syndrome groups by different definitions. Serum RBP4 concentrations were significantly higher with more metabolic disorders. In the highest RBP4 tertile, the MetS risk was significantly higher than in the lowesttertile.
     Conclusion: Each component of metabolic syndrome, except forblood glucose, showed significantly higher serum RBP4 concentrations for both men and women.serum circulating RBP4 concentrations are elevated in human subjects with hyperuricemia. Serum circulating RBP4 concentrations are elevated in human subjects with NAFLD.
     Object: To evaluate serum lipocalin 2 (LCN2) distributions and its association with metabolic syndrome.
     Design: Cross-sectional and case control study.
     Methods: 111 MetS cases and 152 controls were measured serum LCN2 levels with sandwich ELISA.
     Results:①No gender, sex-associated difference in serum LCN2 levels was observed.②Serum LCN2 concentrations were positively correlated with BMI, WC, fat percentage, and hsCRP (P<0.05) after adjusted for sex and age. Serum LCN2 concentrations were negatively correlated with HDL-C (P<0.05). HDL-C and hsCRP were found to be independent determinants for serum LCN2 concentrations.③No difference in serum LCN2 levels was observed between the hypertension and the control group [29.25(10.75-123.25) vs. 28(9.25-92.25) ug/L, P=0.741].④Serum LCN2 concentrations were higher in the obesity group than in the lean and overweight groups [36.37(13-123.25) vs. 29.0(10.75-82.50) vs. 26.75(9.25-86.5) ug/L, P=0.018]. No difference in serum LCN2 levels was observed between the overweight and the lean groups.⑤Serum LCN2 concentrations were no significantly difference between hypertriglyceridemia and control group [29.0(10.75-86.5) vs. 29.0(9.25-123.25)ug/L, P=0.676]. Serum LCN2 concentrations were significantly higher in the hypo-high density lipoproteinemia than the control group [32.62(9.75-82.50) vs. 26.37(9.25-123.25), P=0.001].⑥Serum LCN2 concentrations were higher in the IGT and T2DM groups than in the NGT group [32.5(9.75-89.5) vs. 32.25(9.25-92.25) vs. 27.0(10.75-123.25)ug/L, P=0.008].⑦No difference in serum LCN2 levels was observed between the hyperuricemia and the control group [29.12(9.25-130.25) vs. 30(13-123.25)ug/L, P=0.247].⑧No difference in serum ANGPTL3 levels was observed between the NAFLD and the control group [32.37(9.25-130.25) vs. 28.37(10.75-123.25)ug/L , P=0.134].⑨Serum LCN2 concentrations were significantly higher in the metabolic syndrome than in the control group [32.37(9.25-156.5) vs. 28(10.75-118.25) ug/L, P=0.032]. Serum LCN2 concentrations were all significantly higher in the metabolic syndrome than in the control group under different metabolic syndrome definitions. There was no difference in LCN2 levels among metabolic syndrome groups by different definitions.
     Conclusion: Serum LCN2 concentrations were higher in obesity, T2DM, and metabolic syndrome. Serum lipocalin-2 is independently positively correlated with hsCRP, and can be a useful new marker for evaluating inflammatory status in obesity and MetS.
引文
[1] Executive Summary of The Third Report of The National TCesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood TCesterol In Adults (Adult Treatment Panel Ⅲ). JAMA 2001;285(19): 2486-2497.
    [2] Hutley L, Prins JB. Fat as an endocrine organ: relationship to the metabolic syndrome. Am J Med Sci 2005;330(6): 280-289.
    [3] Lewis GF, Carpentier A, Adeli K, et al. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 2002;23(2): 201-229.
    [1] 中华医学会糖尿病学分会代谢综合征研究协作组。中华医学会糖尿病学分会关于代谢综合征的建议。中华糖尿病杂志,2004:12(3):156-161.
    [2] Executive Summary of the Third Report of the National TCesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood TCesterol in Adults (Adult Treatment Panel III) JAMA. 2001;285(19):2486-2497.
    [3] Scott M. Grundy, MD, PhD, Chair; James I. Cleeman, MD, Co-Chair; Stephen R. Daniels, MD, PhD; Karen A. Donato, MS, RD; Robert H. Eckel, MD; Barry A.Franklin, PhD; David J. Gordon, MD, PhD, MPH; Ronald M. Krauss, MD; Peter J.Savage, MD; Sidney C. Smith, Jr, MD; John A. Spertus, MD; Fernando Costa,MD.Diagnosis and Management of the Metabolic Syndrome: An USA Heart Association/National Heart, Lung, and Blood Institute Scientific Statement: Executive Summary. Circulation. 2005; 112:e285-e290.
    [4] International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. Available from http://www.idf.org/webdate/docs/metabolic
    [5] Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-1197.
    [6] USA Diabetes Association. Standards of Medical Care in Diabetes-2007.Diabetes Care 30:S4-S41.
    [7] Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity, Geneva, 3-5 June, 1997. WHO: Geneva, 1997.
    [8] WHO-ISH Hypertension Guideline committee. 1999 WHO-ISH guideline for the management of hypertension. J Hypertens, 1999;17:151-185
    [9] 中国成人血脂异常防治指南.中华心血管病杂志2007;35(5):390
    [10] 中华医学会肝脏病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南.中华肝脏病杂志2006:14(3):161-163.
    [11] Arita Y, Kihara S, Ouchi N, Takahashi M, et al.Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.Biochem Biophys Res Commun 1999;257:79-83.
    [12] Yang WS, Lee WJ, Funahashi T,et al. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001;86: 3815-3819.
    [13] Takahashi M,Funahashi T, Shimomura I, MiyaokaY, Matsuzawa Y.Plasma leptin levels and body fat distribution. Horm Metab Res 1996;28: 751-752.
    [14] Nop M, Havel PJ, Utzschneider KM, Carr DB,Sinha MK,Boyko EJ,Retzlaff BM, Knopp RH, Brunzell JD, Kahn SE. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003;46: 459-469.
    [15] Atagai T, Nagasaka S,Taniguchi A,et al. (2003) Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus.Metabolism 2003; 52:1274-1278.
    [16] Maeda N, Takahashi M, Funahashi T,et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.Diabetes 2001;50: 2094-2099.
    [17] Hotta K, Funahashi T, AritaY, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595-1599.
    [18] Lindsay RS, Funahashi T, Hanson RL, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002; 360: 57-58.
    [19] Daimon M, Oizumi T, Saitoh T,et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population: the Funagata study. Diabetes Care 2003;26: 2015-2020.
    [20] Yamamoto Y, Hirose H, Saito I, Nishikai K, Saruta T. Adiponectin, an adipocyte-derived protein, predicts future insulin resistance: two year follow-up study in Japanese population. J Clin Endocrinol Metab 2004; 89: 87-90.
    [21] Snehalatha C, MukeshB, Simon M, Viswanathan, V, Haffner SM, Ramachandran A. Plasma adiponectin is an independent predictor of type 2 diabetes in Asian Indians. Diabetes Care 2004;26: 3226-3229.
    [22] Stefan N, Vozarova B, Funahashi T, MatsuzawaY, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA. lasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration and low plasma concentration precedes a decrease in whole body insulin sensitivity in humans" Diabetes 2002;51: 1884-1888.
    [23] Snijder MB, Heine RJ, Seidell JC, BouterLM, Stehouwer CD, Nijpels G, Funahashi T, Matsuzawa Y, Shimomura I, Dekker JM. Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women: the Hoorn study. Diabetes Care 2006;29: 2498-2503.
    [24] Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001;50:1126-1133.
    [25] Adamczak M, Wiecek A, Funahashi T, Chudek J, Koko F, Matsuzawa Y. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens 2003;16: 72-75.
    [26] Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M,Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 2004;43:1318-1323.
    [27] Mallamaci F, Zoccali C, Cuzzola F, Tripepi G Cutrupi S, Parlongo S, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin and essential hypertension. J Nephrol 2002;15:507-511.
    [28] Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A, Hibuse T, Ryo M, Nishizawa H, Maeda N, Maeda K, Shibata R, Walsh K, Funahashi T, Shimomura I. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 2006;47:1108-1116.
    [29] Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 2002; 87:2764-2769.
    [30] Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G. Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL-C size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 2002;25:971-976.
    [31] Hulthe J, Hulten LM, Fagerberg B. Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles: atherosclerosis and insulin resistance study. Metabolism 2003; 52:1612-1614.
    [32] Zietz B, Herfarth H, Paul G, Ehling A, Muller-Ladner U, STCmerich J, Schaffl er A. Adiponectin represents an independent cardiovascular risk factor predicting serum HDLTCesterol levels in type 2 diabetes. FEBS Lett 2003 ;545:103-104.
    [33] Schulze MB, Rimm EB, Shai I, Rifai N, Hu FB. Relationship between adiponectin and glycemic control, blood lipids, and infl ammatory markers in men with type 2 diabetes. Diabetes Care 2004;27:1680-1687.
    [34] Neumeier M, Sigruener A, Eggenhofer E, Weigert J, Weiss TS, Schaeffl er A, Schlitt HJ, Aslanidis C, Piso P, Langmann T, Schmitz G, STCmerich J, Buechler C. High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes. Biochem Biophys Res Commun 2007;352:543- 548.
    [35] Choi KM, Lee J, Lee KW, Seo JA, Oh JH, Kim SG, Kim NH, Choi DS, Baik SH. Serum adiponectin concentrations predict the developments of type 2 diabetes and the metabolic syndrome in elderly Koreans. Clin Endocrinol (Oxf) 2004;61:75-80.
    [36] Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004;68:975-981.
    [37] Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Mohlig M, Pfeiffer AF, Luft FC, Sharma AM. Association between adiponectin and mediators of infl animation in obese women. Diabetes 2003; 52:942-947.
    [38] Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, Okamoto Y, Ohashi K, Nagaretani H, Kishida K, Nishizawa H, Maeda N, Kobayashi H, Hiraoka H, Matsuzawa Y. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 107:671-674.
    [39] Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, Kobes S, Tataranni PA, Hanson RL, Knowler WC, Lindsay RS. Infl ammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care 2003;26:1745-1751.
    [40] Matsubara M, Namioka K, Katayose S. Decreased plasma adiponectin concentrations in women with low-grade C-reactive protein elevation. Eur J Endocrinol 2003;148:657-662.
    [41] Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 2003; 52:1779-1785.
    [42] Pagano C, Esposito W, Plasma adiponectin is decreased in nonalcoholic fatty liver disease. European Journal of Endocrinology 2005;152 (01): 113-118.
    [1] Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH,Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an USA Heart Association/NationalHeart, Lung, and Blood Institute scientific statement [review][published errata appear in Circulation 2005;112:e297 and Circulation 2005;112:e298]. Circulation 2005;112:2735-52.
    [2] Trevisan M, Liu J, Bahsas FB, Menotti A, and the Risk Factorand Life Expectancy Research Group. Syndrome X and mortality: a population-based study. Am J Epidemiol 1998; 148:958-66.
    [3] Shepherd J, Cobbe SM, Ford I, et al. the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hyperTCesterolemia N Engl J Med 1995; 333:1301-1307.
    [4] Conklin D, Gilbertson D, Taft DW, Maurer MF, Whitmore TE, Smith DL, Walker KM, Chen LH, Wattler S, Nehls M, Lewis KB. Identification of a mammalian angiopoietin-related protein expressed specifically in liver. Genomics 1999; 62(3):477-82.
    [5] Ryuta Koishi, Yosuke Ando, Mitsuru Ono, Mitsuru Shimamura, Hiroaki Yasumo, Toshihiko Fujiwara, Hiroyoshi Horikoshi & Hidehiko Furukawa.Angptl3 regulates lipid metabolism in mice. Nature Genetics 2002; 30,151 -157.
    [6] Ando Y, Shimizugawa T, Takeshita S, et al. A decreased expression of angiopoietin-like 3 is protective against atherosclerosis in apoE-deficient mice. J Lipid Res 2003; 44:1216-1223.
    [7] Shimizugawa T, Ono M, Shimamura M, Yoshida K, Ando Y, Koishi R, Ueda K, Inaba T, Minekura H, Kohama T, Furukawa H.ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of Iipoprotein lipase.J Biol Chem. 2002; 277(37):33742-33748.
    [8] Kaplan R, Zhang T, Hernandez M, Gan FX, Wright SD, Waters MG, Cai TQ. Regulation of the angiopoietin-like protein 3 gene by LXR. J Lipid Res 2003 ; 44(1):136-43.
    [9] Shimamura M, Matsuda M, Kobayashi S, Ando Y, Ono M, Koishi R, Furukawa H, Makishima M, Shimomura I.Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes. Biochem Biophys Res Commun 2003; 301(2):604-609.
    [10] Shimizugawa T, Ono M, Shimamura M, Yoshida K, Ando Y, Koishi R, Ueda K,Inaba T, Minekura H, Kohama T, Furukawa H.ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase. J Biol Chem 2002 13; 277(37):33742-33748.
    [11] Sawako Hatsuda, Tetsuo Shoji, Kayo Shinohara, Eiji Kimoto, Katsuhito Mori, Shinya Fukumoto, Hidenori Koyama, Masanori Emoto, Yoshiki Nishizawa. Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects. J Vasc Res 2007; 44:61-66.
    [12] Gieri Camenisch, Maria T. Pisabarro, Daniel Sherman, Joe Kowalski, Mark Nagel, Phil Hass, Austin Gurney, Sarah C. Bodary, Xioa H. Liang, Kevin R. Clark, Maureen H. Beresini, Napoleone Ferrara, and Hans-Peter Gerber. ANGPTL3 stimulates endothelial cell adhesion and migration via integrin aVb3 and induces blood vessel formation in vivo. J. Biol. Chem 2002; 277(19):17281-17290.
    [13] Inukai K, Nakashima Y, Watanabe M, Kurihara S, Awata T, Katagiri H, Oka Y, Katayama S. ANGPTL3 is increased in both insulin-deficient and -resistant diabetic states. Biochem Biophys Res Commun 2004; 317:1075-1079.
    [14] Shimamura M, Matsuda M, Ando Y, Koishi R, Yasumo H, Furukawa H, Shimomura I .Leptin and insulin down-regulate angiopoietin-like protein 3, a plasma triglyceride-increasing factor. Biochem Biophys Res Commun. 2004; 322(3):1080-5.
    [15] Stejskal D, Karp(?)sek M, Humenansk(?) V, Solichov(?) P, Stejskal P. Angiopoietin-like protein 3: development, analytical characterization, and clinical testing of a new ELISA.Gen Physiol Biophys. 2007; 26(3):230-233.
    [1] Erin E. Kershaw, Jeffey S. Flier. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89(6): 2548-2556.
    [2] Tsutsumi C, Okuno M, Tannous L, Piantedosi R, Allan M, Goodman DS, Blaner WS.Retinoids and retinoid-binding protein expression in rat adipocytes. J Biol Chem 1992; 267(3):1805-1810.
    [3] Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005;436:356-362.
    [4] Timothy E. Graham, Qin Yang, Matthias Bl(?)her, Ann Hammarstedt, Theodore P. Ciaraldi, Robert R. Henry, Christopher J. Wason, B.S., Andreas Oberbach, Per-Anders Jansson, Ulf Smith, and Barbara B. Kahn. Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects. N Engl J Med 2006; 354:2552-2563.
    [5] J(?)rgen Janke, Stefan Engeli, Michael Boschmann, Frauke Adams, Jana Bohnke, Friedrich C. Luft, Arya M. Sharma, and Jens Jordan.Retinol-Binding Protein 4 in Human Obesity .Diabetes 2006; 55:2805-2810.
    [6] Young Min Cho, Byung-Soo Youn, et al. Plasma Retinol-Binding Protein-4 Concentrations Are Elevated in Human Subjects With Impaired Glucose Tolerance and Type 2 Diabetes.Diabetes Care 2006;29(ll):2457-2461.
    [7] Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005; 436:356-362.
    [8] Prabhakaran Balagopal, Timothy E. Graham, et al. Reduction of Elevated Serum Retinol Binding Protein in Obese Children by Lifestyle Intervention: Association with Subclinical Inflammation. J Clin Endocrin Metab2007;92(5): 1971-1974
    [9] Dominik G Haider, Karin Schindler, Gerhard Prager, Arthur Bohdjalian, Anton Luger, Michael Wolzt and Bernhard Ludvik .Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab 2007; 92(3): 1168 - 1171
    [10] Lee DC, Lee JW, Im JA. Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents.Metabolism 2007;56(3): 327-331.
    [11] Gavi S, Stuart LM, Kelly P, Melendez MM, Mynarcik DC, Gelato MC, McNurlan MA. Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes. J Clin Endocrinol Metab 2007;92:1886-1890.
    [12] Kohzo Takebayashi, Mariko Suetaugu, et al. Retinol-Binding Protein-4 levels and clinical features of type 2 diabetes patients. J Clin Endocrin Metab 2007; 92(7):2712-2719
    [13]. Qi Q, Yu Z, Ye X, Zhao F, Huang P, Hu FB, Franco OH, Wang J, Li H, Liu Y, Lin X.Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people. J Clin Endocrinol Metab 2007; 92(12):4827-4834.
    [1] KjeldsenL, Johnsen AH, Sengela H et al. Isolation and primary structure of LCN2, a novel protein associated with human neutrophil gelatisase. J Biol Chem 1993; 268(14):10425-10432.
    [2] Qing-Wu Yan, Qin Yang, Nimesh Mody, Timothy E. Graham, Chung-Hsin Hsu, Zhao Xu, NiTCas E. Houstis, Barbara B. Kahn, and Evan D. Rosen .The Adipokine Lipocalin 2 Is Regulated by Obesity and Promotes Insulin Resistance.Diabetes 2007;56:2533-2540.
    [3] Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, Chow WS, Wat NM, Xu JY, Hoo RL, Xu A. Lipocalin 2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 2007 ; 53(1):34-41.
    [4] Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.Nature 2004;432(7019):917-921.
    [5] Laxminarayana R. Devireddy, Jose G. Teodoro, Fabien A. Richard, and Michael R. Green .Induction of Apoptosis by a Secreted Lipocalin That is Transcriptionally Regulated by IL-3 Deprivation. Science 2001; 293(5531): 829 - 834.
    [6] Kratchmarova I, Kalume DE, Blagoev B, Scherer PE, Podtelejnikov AV, Molina H, Bickel PE, Andersen JS, Fernandez MM, Bunkenborg J, Roepstorff P, Kristiansen K, Lodish HF, Mann M, Pandey A. A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes. Mol Cell Proteomics 2002;l(3):213-222.
    [7] Meheus LA, Fransen, LM JG Raymackers, HA Blockx, JJ Van Beeumen, SM Van Bun and A Van de Voorde. Identification by microsequencing of lipopolysaccharide-induced proteins secreted by mouse macrophages . J Immunol. 1993;151(3):1535-1547.
    [8] Soukas A, Cohen P, Socci ND,et al. Leptin-specific patterns of gene expression in white adipose tissue. Genes Dev 2000; 14: 963-980.
    [9] Lin Y, Rajala MW, Berger JP, et al.Hyperglycemia-induced production of acute phase reactants in adipose tissue.Biolog Chem 2001; 11:42077-42083.
    [10] Grundy SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardio 2006;197:3A-11A.
    [1] World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: i-xii, 1-253.
    [2] Reaven GM, Banting lectures. Role of insulin resistance in human disease. Diabetes 1988; 37 (12): 1595-1607.
    [3] Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994; 17 (9) :961-969.
    [4] Han TS, Feskens EJ, Lean ME et al. Associations of body composition with type 2 diabetes mellitus. Diabet Med 1998; 15 (2):129-135.
    [5] Grundy SM, Brewer HB, and Cleeman JI, et al. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/USA Heart Association conference on scientific issues related to definition. Circulation 2004; 109 (3) :433-438.
    [6] Qatanani M, Lazar MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev 2007; 21 (12):1443-1455.
    [7] Savage DB, Petersen KF, Shulman GI. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 2007; 87 (2) :507-520.
    [8] Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006; 116 (7): 1793-1801.
    [9] Frayn KN. Adipose tissue and the insulin resistance syndrome. Proc Nutr Soc 2001; 60 (3):375-380.
    [10] Forouhi NG, Jenkinson G, Thomas EL, et al. Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men. Diabetologia 1999; 42 (8):932-935.
    [11] Jacob S, Machann J, Rett K, Brechtel K, et al. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes 1999; 48 (5):1113-1119.
    [12] Pan DA, Lillioja S, Kriketos AD, et al. Skeletal muscle triglyceride levels are inversely related to insulin action, Diabetes 46 (6) (1997), pp. 983-988.
    [13] Koyama K, Chen G, Lee Y, et al. Tissue triglycerides, insulin resistance, and insulin production: implications for hyperinsulinemia of obesity. Am J Physiol 1997; 273 (4 Pt 1): E708-E713.
    [14] Banerji MA, MC Buckley, Chaiken RL, et al.Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NIDDM. Int J Obes Relat Metab Disord 1995; 19 (12): 846-850.
    [15] Bjorntorp P, liver triglycerides and metabolism. Int J Obes Relat Metab Disord 1995; 19 (12):839-840.
    [16] Fanelli C, Calderone S, Epifano L, et al. Demonstration of a critical role for free fatty acids in mediating counterregulatory stimulation of gluconeogenesis and suppression of glucose utilization in humans. J Clin Invest 1993; 92 (4): 1617-1622.
    [17] Ferrannini E, Barrett EJ, Bevilacqua S, et al. Effect of fatty acids on glucose production and utilization in man. J Clin Investl983; 72 (5):1737-1747.
    [18] Lewis GF, Vranic M, Harley P, et al .and A. Fatty acids mediate the acute extra hepatic effects of insulin on hepatic glucose production in humans. Diabetes 1997; 46 (7):1111-1119.
    [19] Byrne CD, Brindle NP, Wang TW ,et al., Interaction of non-esterified fatty acid and insulin in control of triacylglycerol secretion by Hep G2 cells. Biochem J 1991; 280 (Pt 1):99-104.
    [20] Hermes MM, Dua A, Kissebah AH. Effects of free fatty acids and glucose on splanchnic insulin dynamics. Diabetes 1997; 46 (1): 57-62.
    [21] Svedberg J, Bjorntorp P, Smith U, et al. Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes. Diabetes 1990; 39 (5): 570-574.
    [22] Wiesenthal SR, Sandhu H, RH McCall, et al, Free fatty acids impairs hepatic insulin extraction in vivo. Diabetes 1999; 48 (4):766-774.
    [23] Frayn KN, Williams CM, Arner P. Are increased plasma non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases? Clin Sci (Lond) 1996; 90 (4):243-253.
    [24] Ganda OP. lipoatrophy and insulin resistance. Ann Intern Med 2000; 133 (4): 304-306.
    [25] Kim JK, Gavrilova O, Chen Y, et al. Mechanism of insulin resistance in A-ZIP/F-1 fatless mice. J Biol Chem 2000; 275 (12):8456-8460.
    [26] Gavrilova O, Marcus-Samuels B, Graham D, et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest 2000; 105 (3): 271-278.
    [27] Baron AD and Clark MG. Role of blood flow in the regulation of muscle glucose uptake. Annu Rev Nutr 1997; 17:487-499.
    [28] Bulow J and Madsen J. Influence of blood flow on fatty acid mobilization form lipolytically active adipose tissue. Pflugers Arch 1981; 390 (2):169-174.
    [29] Galitzky J, Lafontan M, Nordenstrom J, et al. Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue. J Clin Invest 1993; 91 (5): 1997-2003.
    [30] Samra JS, Simpson EJ, Clark ML, et al. Effects of epinephrine infusion on adipose tissue: interactions between blood flow and lipid metabolism. Am J Physiol 1996; 271 (5 Pt 1):E834-E839.
    [31] Ardilouze JL, Fielding BA, Currie JM, et al. Nitric oxide and beta-adrenergic stimulation are major regulators of preprandial and postprandial subcutaneous adipose tissue blood flow in humans. Circulation 2004; 109 (1):47-52.
    [32] Ardilouze JL, Karpe F, Currie JM, et al. Subcutaneous adipose tissue blood flow varies between superior and inferior levels of the anterior abdominal wall. Int J Obes Relat Metab Disord 2004; 28 (2): 228-233.
    [33] Bulow J, Astrup A, Christensen NJ et al. Blood flow in skin, subcutaneous adipose tissue and skeletal muscle in the forearm of normal man during an oral glucose load. Acta Physiol Scand 1987; 130 (4):657-661.
    [34] Coppack SW, Evans RD, Fisher RM, et al. Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal.Metabolism 1992; 41 (3) :264-272.
    [35] Evans K, Clark ML and Frayn KN. Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism. Am J Physiol 1999 276 (2 Pt 1):E241-E248.
    [36] Goossens GH, McQuaid SE, Dennis AL, et al. Angiotensin Ⅱ: a major regulator of subcutaneous adipose tissue blood flow in humans. J Physiol 2006; 571 (Pt 2): 451-460.
    [37] Frayn KN, Karpe F, Fielding BA, et al. Integrative physiology of human adipose tissue. Int J Obes Relat Metab Disord 2003; 27 (8):875-888.
    [38] Blaak EE, van Baak MA, Kemerink GJ, et al. Beta-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjects. Metabolism 1995; 44 (2):183-187.
    [39] Goossens GH, Jocken JW, Blaak EE, et al. Endocrine role of the renin-angiotensin system in human adipose tissue and muscle: effect of beta-adrenergic stimulation. Hypertension 2007; 49 (3):542-547.
    [40] Jansson PA, Larsson A and Lonnroth PN. Relationship between blood pressure, metabolic variables and blood flow in obese subjects with or without non-insulin-dependent diabetes mellitus. Eur J Clin Invest 1998; 28 (10): 813-818.
    [41] Summers LK, Samra JS, Humphreys SM, et al. Subcutaneous abdominal adipose tissue blood flow: variation within and between subjects and relationship to obesity. Clin Sci (Lond) 1996; 91 (6):679-683.
    [42] Virtanen KA, Lonnroth P, Parkkola R, et al. Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans. J Clin Endocrinol Metab 2002; 87 (8):3902-3910.
    [43] Karpe F, Fielding BA, Ilic V, et al. summers and K.N. Frayn, Impaired postprandial adipose tissue blood flow response is related to aspects of insulin sensitivity. Diabetes 2002; 51 (8): 2467-2473.
    [44] Potts JL, Coppack SW, Fishe r RM, et al. Impaired postprandial clearance of triacylglycerol-rich lipoproteins in adipose tissue in obese subjects. Am J Physiol 1995; 268 (4 Pt 1): E588-E594.
    [45] Baron AD, Insulin resistance and vascular function. J Diabetes Complications 2002; 16 (1):92-102.
    [46] Baron AD, Steinberg HO, Chaker H, et al. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J Clin Invest 1995; 96 (2): 786-792.
    [47] Yudkin JS, Eringa E, and Stehouwer CD, "Vasocrine" signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease, Lancet 2005; 365 (9473): 1817-1820.
    [48] Eriksson JW, Smith U, Waagstein F, et al. Glucose turnover and adipose tissue lipolysis are insulin-resistant in healthy relatives of type 2 diabetes patients: is cellular insulin resistance a secondary phenomenon? Diabetes 1999; 48 (8): 1572-1578.
    [49] Paolisso G, Tataranni PA, Foley JE, et al. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 1995; 38 (10):1213-1217.
    [50] Weyer C, Foley JE, Bogardus C, et al. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 2000; 43 (12): 1498-1506.
    [51] Weyer C, Wolford JK, Hanson RL, et al. Subcutaneous abdominal adipocyte size, a predictor of type 2 diabetes, is linked to chromosome Iq21-q23 and is associated with a common polymorphism in LMNA in Pima Indians. Mol Genet Metab 2001; 72 (3): 231-238.
    [52] Lundgren M, Svensson M, Lindmark S, et al. Fat cell enlargement is an independent marker of insulin resistance and 'hyperleptinaemia', Diabetologia 2007; 50 (3): 625-633.
    [53] Holm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans 2003; 31 (6): 1120-1124.
    [54] Zimmermann R, Strauss JG, Haemmerle G, et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004; 306 (5700): 1383-1386.
    [55] Arner P, Bolinder J, Engfeldt P, et al. Influence of obesity on the antilipolytic effect of insulin in isolated human fat cells obtained before and after glucose ingestion. J Clin Invest 1984; 73 (3): 673-680.
    [56] Lonnroth P, Digirolamo M, Krotkiewski M, et al. Insulin binding and responsiveness in fat cells from patients with reduced glucose tolerance and type Ⅱ diabetes. Diabetes 1983; 32 (8): 748-754.
    [57] Tan GD, Fielding BA, Currie JM, et al. The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 2005; 48 (1): 83-95.
    [58] Karpe F and Tan GD. Adipose tissue function in the insulin-resistance syndrome. Biochem Soc Trans 2005; 33 (5): 1045-1048.
    [59] Buren J, lindmark S, Renstrom F, et al. In vitro reversal of hyperglycemia normalizes insulin action in fat cells from type 2 diabetes patients: is cellular insulin resistance caused by glucotoxicity in vivo? Metabolism 2003; 52 (2):239-245.
    [60] Czech MP. Cellular basis of insulin insensitivity in large rat adipocytes. J Clin Invest 1976; 57 (6): 1523-1532.
    [61] Karnieli E, Barzilai A, Rafaeloff R, et al. Distribution of glucose transporters in membrane fractions isolated from human adipose cells Relation to cell size. J Clin Invest 1986; 78 (4):1051-1055.
    [62] Olefsky JM. Insensitivity of large rat adipocytes to the antilipolytic effects of insulin. J Lipid Res 1977; 18 (4):459-464.
    [63] Olefsky JM. Mechanisms of decreased insulin responsiveness of large adipocytes. Endocrinology 1977; 100 (4): 1169-1177.
    [64] Shepherd PR, Gnudi L, Tozzo E, et al. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J Biol Chem 1993; 268 (30): 22243-22246.
    [65] DeFronzo RA, Jacot E, Jequier E, et al. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 1981; 30 (12):1000-1007.
    [66] Souza CJ de, Eckhardt M, Gagen K, et al. Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance. Diabetes 2001; 50 (8): 1863-1871.
    [67] Hallakou S, Doare L, Foufelle F, et al. Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes 1997; 46 (9): 1393-1399.
    [68] Okuno A, Tamemoto H, Tobe K, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 1998; 101 (6): 1354-1361.
    [69] Crossno Jr JT, Majka SM, Grazia T, et al. Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. J Clin Invest 2006; 116 (12): 3220-3228.
    [70] Minoura H, Takeshita S, Kimura C, Hirosumi J, et al. Proliferator-activated receptor gamma agonist, FK614, ameliorates insulin resistance in Zucker fatty rats. Diabetes Obes Metab 2007; 9 (3): 369-378.
    [71] Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, et al.The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 2001; 280 (6): E827-E847.
    [72] Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89 (6): 2548-2556.
    [73] Bastard JP, Maachi M, Lagathu C, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006; 17 (1): 4-12.
    [74] Engstrom G, Hedblad B, Stavenow L, et al. Inflammation-sensitive plasma proteins are associated with future weight gain. Diabetes 2003; 52 (8): 2097-2101.
    [75] Festa A, D'Agostino JR, Howard G, et al. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000; 102 (1): 42-47.
    [76] Yudkin JS. Adipose tissue, insulin action and vascular disease: inflammatory signals. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3): S25-S28.
    [77] Bastard JP, Jardel C, Bruckert E, Blondy P, et al. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 2000; 85 (9):3338-3342.
    [78] Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 2003; 285 (3): E527-E533.
    [79] Hotamisligil GS, Arner P, Caro JF, R.L. Atkinson and B.M. Spiegelman, Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995; 95 (5): 2409-2415.
    [80] Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 107 (5):671-674.
    [81] Rotter V, Nagaev I and Smith U, Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003; 278 (46): 45777-45784.
    [82] Hotamisligil GS and Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 1994; 43 (11):1271-1278.
    [83] Kern PA, Ranganathan S, C Li, et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001; 280 (5): E745-E751.
    [84] Maachi M, Pieroni L, Bruckert E, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 2004; 28 (8): 993-997.
    [85] Fried SK, Bunkin DA and Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998; 83 (3): 847-850.
    [86] Mohamed-Ali V, Goodrick S, Rawesh A, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997; 82 (12): 4196-4200.
    [87] Alessi MC, Bastelica D, Morange P, et al. Plasminogen activator inhibitor 1, transforming growth factor-betal, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 2000; 49 (8): 1374-1380.
    [88] Alessi MC, Poggi M and Juhan-Vague I. Plasminogen activator inhibitor-1, dipose tissue and insulin resistance. Curr Opin Lipidol 2007; 18 (3): 240-245.
    [89] Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334 (5): 292-295.
    [90] Klein S, Coppack SW, Mohamed-Ali V, et al. Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes 1996; 45 (7): 984-987.
    [91] Ostlund Jr RE, Yang JW, S Klein and R Gingerich. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 1996; 81 (11): 3909-3913.
    [92] Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257 (1): 79-83.
    [93] Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20 (6):1595-1599.
    [94] Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86 (5): 1930-1935.
    [95] Guo KY, Halo P, Leibel RL and Zhang Y, Effects of obesity on the relationship of leptin mRNA expression and adipocyte size in anatomically distinct fat depots in mice. Am J Physiol Regul Integr Comp Physiol 2004; 287 (1): R112-R119.
    [96] Hamilton BS, Paglia D, Kwan AY, et al. Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med 1995; 1 (9): 953-956.
    [97] Jernas M, Palming J, and Sjoholm K, et al. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. FASEB J 2006; 20 (9): 1540-1542.
    [98] Skurk T, Alberti-Huber C, Herder C, et al. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92 (3): 1023-1033.
    [99] Lofgren P, Andersson I, Adolfsson B, et al. Long-term prospective and controlled studies demonstrate adipose tissue hypercellularity and relative leptin deficiency in the post-obese state. J Clin Endocrinol Metab 2005; 90: 6207-6213.
    [100] Degawa-Yamauchi M, Moss KA, Bovenkerk JE, et al. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor alpha. Obes Res 2005; 13 (4): 662-669.
    [101] Sopasakis VR, Sandqvist M, Gustafson B, et al. High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator. Obes Res 2004; 12 (3): 454-460.
    [102] Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta 2007; 380 (1-2): 24-30.
    [103] Grunfeld C, Feingold KR, The metabolic effects of tumor necrosis factor and other cytokines. Biotherapy 1991; 3 (2):143-158.
    [104] Ruan H, Hacohen N, Golub TR, et al. Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes 2002; 51 (5): 1319-1336.
    [105] Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 2001; 60 (3):349-356.
    [106] Corpeleijn E, Saris WH, Jansen EH, et al. Postprandial interleukin-6 release from skeletal muscle in men with impaired glucose tolerance can be reduced by weight loss. J Clin Endocrinol Metab 2005; 90 (10): 5819-5824.
    [107] Pedersen BK, Fischer CP. Physiological roles of muscle-derived interleukin-6 in response to exercise. Curr Opin Clin Nutr Metab Care 2007; 10 (3): 265-271.
    [108] Pedersen BK, Steensberg A and Schjerling P. Muscle-derived interleukin-6: possible biological effects. J Physiol 2001; 536 (Pt 2): 329-337.
    [109] Steensberg A, van Hall G, Osada T, et al. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6.J Physiol 2000; 529 (Pt 1): 237-242.
    [110] Yudkin JS, Kumari M, Humphries SE, et al. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000; 148 (2): 209-214.
    [111] Yudkin JS, Stehouwer CD, Emeis JJ, et al. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19 (4): 972-978.
    [112] Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 2005; 11 (2): 183-190.
    [113] Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance. Nature 2002; 420 (6913): 333-336.
    [114] Perreault M and Marette A. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 2001; 7 (10): 1138-1143.
    [115] Uysal KT, Wiesbrock SM, Marino MW, et al. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 1997; 389 (6651): 610-614.
    [116] Yuan M, Konstantopoulos N, Lee J, et al., Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001; 293 (5535): 1673-1677.
    [117] Petruschke T and H. Hauner. Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells. J Clin Endocrinol Metab 1993; 76 (3): 742-747.
    [118] Stephens JM and PH Pekala. Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha: Regulations is coordinate and independent of protein synthesis. J Biol Chem 1992; 267 (19): 13580-13584.
    [119] Hong X, Jeffrey P. Northrop, Russell J. Grove, et al. TNF alpha-mediated inhibition and reversal of adipocyte differentiation is accompanied by suppressed expression of PPARgamma without effects on Pref-1 expression. Endocrinology 1997; 138 (7): 2776-2783.
    [120] Prins JB, Niesler CU, Winterford CM, et al. Tumor necrosis factor-alpha induces apoptosis of human adipose cells. Diabetes 1997; 46 (12): 1939-1944.
    [121] Hauner H, Petruschke T, Russ M, et al. Effects of tumour necrosis factor alpha (TNF alpha) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture. Diabetologia 1995; 38 (7): 764-771.
    [122] Souza SC, Palmer HJ, Kang YH, et al. TNF-alpha induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3-L1 adipocytes. J Cell Biochem 2003; 89 (6):1077-1086.
    [123] Zhang HH, Halbleib M, Ahmad F, et al.Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 2002; 51 (10): 2929-2935.
    [124] Su CL, Sztalryd C, Contreras JA, et al. Mutational analysis of the hormone-sensitive lipase translocation reaction in adipocytes. J Biol Chem 2003; 278 (44): 43615-43619.
    [125] van Hall G, Steensberg A, Sacchetti M, et al. Schjerling et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab 2003; 88 (7): 3005-3010.
    [126] Tomas E, Tsao TS, Saha AK, et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci 2002; 99(25): 16309-16313.
    [127] Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423 (6941): 762-769.
    [128] Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8 (11): 1288-1295.
    [129] de Alvaro C, Teruel T, Hernandez R, et al. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner. J Biol Chem 2004; 279 (17): 17070-17078.
    [130] Hotamisligil GS, Inflammatory pathways and insulin action. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3): S53-S55.
    [131] Ceddia RB, Somwar R, Maida A, et al. Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia 2005; 48 (1): 132-139.
    [132] Mao X, Kikani CK, RA Riojas, et al. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol 2006; 8 (5): 516-523.
    [133] Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112 (12):1796-1808.
    [134] Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112 (12): 1821-1830.
    [135] Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 2006; 74: 443-477.
    [136] Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54 (8): 2277-2286.
    [137] Curat CA, Wegner V, Sengenes C, et al. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 2006; 49 (4): 744-747.
    [138] Di Gregorio GB, Yao-Borengasser A, Rasouli N, et al. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes 2005; 54 (8): 2305-2313.
    [139] Clement K, Viguerie N, Poitou C, et al. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J 2004; 18 (14):1657-1669.
    [140] Permana PA, Menge C and Reaven PD. Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. Biochem Biophys Res Commun 2006; 341 (2):507-514.
    [141] Lacasa D, Taleb S, Keophiphath M, et al. Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology 2007; 148 (2): 868-877.
    [142] Gordon S and Taylor PR, Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005; 5 (12): 953-964.
    [143] Mantovani A, Sica A, Sozzani S, et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25 (12): 677-686.
    [144] Lumeng CN, Deyoung SM, Bodzin JL, et al. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 2007; 56 (1): 16-23.
    [145] Baggiolini M. Chemokines and leukocyte traffic. Nature 1998; 392 (6676): 565-568.
    [146] Christiansen T, Richelsen B and Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes (Lond) 2005; 29 (1): 146-150.
    [147] Gerhardt CC, Romero IA, R Cancello, L. Camoin and A.D. Strosberg, Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol 2001; 175 (1-2): 81-92.
    [148] Bruun JM, Lihn AS, Pedersen SB, et al. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J Clin Endocrinol Metab 2005; 90 (4): 2282-2289.
    [149] Sartipy P and Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA 2003; 100 (12): 7265-7270.
    [150] Takahashi K, Mizuarai S, Araki H, et al. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem 2003; 278 (47): 46654-46660.
    [151] Kim CS, Park HS, Kawada T, et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond) 2006; 30 (9): 1347-1355.
    [152] Nomura S, Shouzu A, Omoto S, et al. Significance of chemokines and activated platelets in patients with diabetes. Clin Exp Immunol 2000; 121 (3): 437-443.
    [153] Piemonti L, Calori G, Mercalli A, et al. Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality. Diabetes Care 2003; 26 (10): 2883-2889.
    [154] Schernthaner GH, Kopp HP, Kriwanek S, et al. Effect of massive weight loss induced by bariatric surgery on serum levels of interleukin-18 and monocyte-chemoattractant-protein-1 in morbid obesity. Obes Surg 2006; 16 (6): 709-715.
    [155] Sell H, Dietze-Schroeder D, Kaiser U et al. Monocyte chemotactic protein-1 is a potential player in the negative cross-talk between adipose tissue and skeletal muscle. Endocrinology 2006; 147 (5): 2458-2467.
    [156] Herder C, Muller-Scholze S, Rating P, et al. Systemic monocyte chemoattractant protein-1 concentrations are independent of type 2 diabetes or parameters of obesity: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Eur J Endocrinol 2006; 154 (2): 311-317.
    [157] Fasshauer M, Klein J, Kralisch S, et al. Monocyte chemoattractant protein 1 expression is stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2004; 317 (2): 598-604.
    [158] Ping D, Jones PL and Boss JM. TNF regulates the in vivo occupancy of both distal and proximal regulatory regions of the MCP-l/JE gene. Immunity 1996; 4 (5): 455-469.
    [159] Dietze-Schroeder D, Sell H, Uhlig M, et al. Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors. Diabetes 2005; 54 (7): 2003-2011.
    [160] Sell H, Dietze-Schroeder D, Eckardt K, et al. Cytokine secretion by human adipocytes is differentially regulated by adiponectin, AICAR, and troglitazone. Biochem Biophys Res Commun 2006; 343 (3): 700-706.
    [161] Kanda H, Tateya S, Tamori Y, et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006; 116 (6): 1494-1505.
    [162] Weisberg SP, Hunter D, R Huber, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006; 116 (1): 115-124.
    [163] Kamei N, Tobe K, Suzuki R, et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 2006; 281 (36): 26602-26614.
    [1] Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M , Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79-83.
    [2] Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, Chen CL, Tai TY, Chuang LM.Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin.J Clin Endocrinol Metab 2001; 86: 3815-3819.
    [3] Takahashi M, Funahashi T, Shimomura I, Miyaoka Y, Matsuzawa Y .Plasma leptin levels and body fat distribution. Horm Metab Res 1996; 28: 751-752.
    [4] Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, Retzlaff BM, Knopp RH, Brunzell JD, Kahn SE. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003; 46: 459-469.
    [5] YatagaiT, Nagasaka S, Taniguchi A, Fukushima M, Nakamura T, Kuroe A, Nakai Y, Ishibashi S .Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus. Metabolism 2003; 52:1274-1278.
    [6] Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 2001;50: 2094-2099.
    [7] Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Matsuzawa Y. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003; 23: 85-89.
    [8] Zoccali C, Mallamaci F, Tripepi G, Benedetto FAQ, Cutrupi S, Parlongo S, Malatino LS, Monanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 2002; 13:134-141.
    [9] Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291: 1730-1737.
    [10] HottaK, Funahashi T, AritaY, Takahashi M, MatsudaM, OkamotoY, Iwahashi H, KuriyamaH, OuchiN, MaedaK, NishidaM, KiharaS, SakaiN, NakajimaT, Hasegawa K, Muraguchi M, OhmotoY, NakamuraT, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20:1595-1599.
    [11] Kojima S, Funahashi T, Maruyoshi H, Honda O, Sugiyama S, Kawano H, Soejima H, Miyamoto S, Hokamaki J, Sakamoto T, Yoshimura M, Kitagawa A, Matsuzawa Y, Ogawa H. Levels of the adipocyte-derived plasma protein, adiponectin, have a close relationship with atheroma. Thromb Res 2005; 115: 483-490.
    [12] Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100: 2473-2476.
    [13] Nakamura Y, Shimada K, Fukuda D, Shimada Y, Ehara S, Hirose M, Kataoka T, Kamimori K, Shimodozono S, Kobayashi Y, Yoshiyama M, Takeuch K, Yoshikawa J. Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart 2004; 90: 528-533.
    [14] OtsukaF, Sugiyama S, Kojima S, Maruyoshi H, Funahashi T, Matsui K, Sakamoto T, Yoshimura M, Kimura K, Umemura S, Ogawa H. Plasma adiponectin levels are associated with coronary lesion complexity in men with coronary artery disease. J Am Coll Cardiol 2006; 48:1155-1162.
    [15] Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, Knowler WC, Krakoff J. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002; 360: 57-58.
    [16] Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H, Ohnuma H, Igarashi M, Tominaga M, Kato T. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population: the Funagata study. Diabetes Care 2003; 26: 2015-2020.
    [17] Yamamoto Y, Hirose H, Saito I, Nishikai K, Saruta T. Adiponectin, an adipocyte-derived protein, predicts future insulin resistance: two year follow-up study in Japanese population. J Clin Endocrinol Metab 2004; 89: 87-90.
    [18] SnehalathaC, MukeshB, Simon M, Viswanathan, V, HaffnerSM, Ramachandran A. Plasma adiponectin is an independent predictor of type 2 diabetes in Asian Indians. Diabetes Care 2004; 26: 3226-3229.
    [19] Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA. lasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration and low plasma concentration precedes a decrease in whole body insulin sensitivity in humans" Diabetes 2002; 51: 1884-1888.
    [20] Snijder MB, Heine RJ, Seidell JC, Bouter LM, Stehouwer CD, Nijpels G, Funahashi T, Matsuzawa Y, Shimomura I, Dekker JM. Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women: the Hoorn study. Diabetes Care 2006; 29: 2498-2503.
    [21] Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001; 50: 1126-1133.
    [22] Adamczak M, Wiecek A, Funahashi T, Chudek J, Koko F, Matsuzawa Y. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens 2003; 16:72-75.
    [23] Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M,Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 2004; 43:1318-1323.
    [24] Mallamaci F, Zoccali C, Cuzzola F, Tripepi G, Cutrupi S, Parlongo S, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin and essential hypertension. J Nephrol 2002; 15:507-511.
    [25] Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A, Hibuse T, Ryo M, Nishizawa H, Maeda N, Maeda K, Shibata R, Walsh K, Funahashi T, Shimomura I. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 2006; 47:1108-1116.
    [26] Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 2002; 87:2764-2769
    [27] Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G. Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 2002; 25:971- 976.
    [28] Hulthe J, Hulten LM, Fagerberg B. Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles: atherosclerosis and insulin resistance study. Metabolism 2003; 52:1612-1614.
    [29] Zietz B, Herfarth H, Paul G, Ehling A, Muller-Ladner U, Scholmerich J, Schaffl er A. Adiponectin represents an independent cardiovascular risk factor predicting serum HDL-Ccholesterol levels in type 2 diabetes. FEBS Lett 2003; 545:103-104
    [30] Schulze MB, Rimm EB, Shai I, Rifai N, Hu FB. Relationship between adiponectin and glycemic control, blood lipids, and infl ammatory markers in men with type 2 diabetes. Diabetes Care 2004; 27:1680-1687.
    [31] Neumeier M, Sigruener A, Eggenhofer E, Weigert J, Weiss TS, Schaeffl er A, Schlitt HJ, Aslanidis C, Piso P, Langmann T, Schmitz G, Scholmerich J, Buechler C. High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes. Biochem Biophys Res Commun 2007; 352:543- 548.
    [32] Choi KM, Lee J, Lee KW, Seo JA, Oh JH, Kim SG, Kim NH, Choi DS, Baik SH. Serum adiponectin concentrations predict the developments of type 2 diabetes and the metabolic syndrome in elderly Koreans. Clin Endocrinol (Oxf) 2004; 61:75-80.
    [33] Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004; 68:975-981.
    [34] Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Mohlig M, Pfeiffer AF, Luft FC, Sharma AM. Association between adiponectin and mediators of infl animation in obese women. Diabetes 2003; 52:942-947.
    [35] Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, Okamoto Y, Ohashi K, Nagaretani H, Kishida K, Nishizawa H, Maeda N, Kobayashi H, Hiraoka H, Matsuzawa Y. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 107:671- 674.
    [36] Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, Kobes S, Tataranni PA, Hanson RL, Knowler WC, Lindsay RS. Infl ammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care 2003; 26:1745- 1751.
    [37] Matsubara M, Namioka K, Katayose S. Decreased plasma adiponectin concentrations in women with low-grade C-reactive protein elevation. Eur J Endocrinol 2003; 148:657-662.
    [38] Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 2003; 52:1779-1785.
    [39] Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y. An adipocytederived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 2002; 32:47-50.
    [40] Shimabukuro M, Higa N, Asahi T, Oshiro Y, Takasu N, Tagawa T, Ueda S, Shimomura I, Funahashi T, Matsuzawa Y. Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J Clin Endocrinol Metab 2003; 88:3236-3240.
    [41] Tan KC, Xu A, Chow WS, Lam MC, Ai VH, Tam SC, Lam KS. Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab 2004; 89:765-769
    [42] Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 2003; 278:45021-45026.
    [43] Ouchi N, Ohishi M, Kihara S, Funahashi T, Nakamura T, Nagaretani H, Kumada M, Ohashi K, Okamoto Y, Nishizawa H, Kishida K, Maeda N, Nagasawa A, Kobayashi H, Hiraoka H, Komai N, Kaibe M, Rakugi H, Ogihara T, Matsuzawa Y. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 2003; 42:231-234.
    [44] Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y. 0 Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103:1057-1063.
    [45] Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, Maeda K, Nagaretani H, Kishida K, Maeda N, Nagasawa A, Funahashi T, Matsuzawa Y. Adiponectin specifi cally increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004; 109:2046-2049.
    [46] Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, Kumada M, Hotta K, Nishida M, Takahashi M, Nakamura T, Shimomura I, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation 2002; 105:2893-2898.
    [47] Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004; 24:29-33
    [48] Combs TP, Berg AH, Obici S, Scherer PE, and Rossetti L. Endogenous glucose production is inhibited by the adiposederived protein Acrp30. J Clin Invest 2001; 108:1875-1881
    [49] Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8:1288-1295
    [50] Stefan N, Stumvoll M, Vozarova B, Weyer C, Funahashi T, Matsuzawa Y, Bogardus C, Tataranni PA. Plasma adiponectin and endogenous glucose production in humans. Diabetes Care 2003; 26:3315-3319
    [51] Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98:2005-2010
    [52] Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7:941-946
    [53] Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002; 106:2767-2770
    [54] Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Adiponectin, an adipocyte-derived plasma protein,inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway.Circulation 2000; 102:1296-1301
    [1] Conklin D, Gilbertson D, Taft DW, Maurer MF, Whitmore TE, Smith DL, Walker KM, Chen LH, Wattler S, Nehls M, Lewis KB. Identification of a mammalian angiopoietin-related protein expressed specifically in liver. Genomics 1999;62(3): 477-482.
    [2] Shimizugawa T, Ono M, Shimamura M, Yoshida K, Ando Y, Koishi R, Ueda K, Inaba T, Minekura H, Kohama T, Furukawa H. ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase.J Biol Chem 2002; 277(37): 33742-33748.
    [3] Kaplan R, Zhang T, Hernandez M, Gan FX, Wright SD, Waters MG, Cai TQ. Regulation of the angiopoietin-like protein 3 gene by LXR. J lipid Res 2003; 44(1):136-143.
    [4] Ryuta Koishi, Yosuke Ando, Mitsuru Ono, Mitsuru Shimamura, Hiroaki Yasumo, Toshihiko Fujiwara, Hiroyoshi Horikoshi & Hidehiko Furukawa. Angpt13 regulates lipid metabolism in mice. Nature Genetics 2002; 30,151-157.
    [5] Shimamura M, Matsuda M, Kobayashi S, Ando Y, Ono M, Koishi R, Furukawa H, Makishima M, Shimomura I. Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes. Biochem Biophys Res Commun 2003; 301(2):604-609.
    [6] Shimizugawa T, Ono M, Shimamura M, Yoshida K, Ando Y, Koishi R, Ueda K, Inaba T, Minekura H, Kohama T, Furukawa H.ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase. J Biol Chem 2002; 277(37):33742-33748.
    [7] Ando Y, Shimizugawa T, Takeshita S, et al. A decreased expression of angiopoietin-like 3 is protective against atherosclerosis in apoE-deficient mice. J Lipid Res 2003; 44:1216-1223.
    [8] Sawako Hatsuda, Tetsuo Shoji, Kayo Shinohara, Eiji Kimoto, Katsuhito Mori, Shinya Fukumoto, Hidenori Koyama, Masanori Emoto, Yoshiki Nishizawa. Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects J Vasc Res 2007; 44:61-66.
    [9] Gieri Camenisch, Maria T. Pisabarro, Daniel Sherman, Joe Kowalski, Mark Nagel, Phil Hass, Austin Gurney, Sarah C. Bodary, Xioa H. Liang, Kevin R. Clark, Maureen H. Beresini, Napoleone Ferrara, and Hans-Peter Gerber. ANGPTL3 stimulates endothelial cell adhesion and migration via integrin aVb3 and induces blood vessel formation in vivo. J. Biol. Chem 277(19):17281-17290.
    [10] Inukai K, Nakashima Y, Watanabe M, Kurihara S, Awata T, Katagiri H, and Oka Y, Katayama S: ANGPTL3 is increased in both insulin-deficient and -resistant diabetic states. Biochem Biophys Res Commun 2004; 317:1075-1079.
    [11] Shimamura M, Matsuda M, Ando Y, Koishi R, Yasumo H, Furukawa H, Shimomura I .Leptin and insulin down-regulate angiopoietin-like protein 3, a plasma triglyceride-increasing factor. Biochem Biophys Res Commun 2004 ; 322(3):1080-1085.
    [12] Stejskal D, Karp(?)sek M, Humenanska V, Solichova P, Stejskal P.Angiopoietin-like protein 3: development, analytical characterization, and clinical testing of a new ELISA.Gen Physiol Biophys. 2007; 26(3):230-233.
    [1] Tsutsumi C, Okuno M, Tannous L, Piantedosi R, Allan M, Goodman DS, Blaner WS.Retinoids and retinoid-binding protein expression in rat adipocytes. J Biol Chem. 1992;267(3):1805-1810.
    [2] Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005;436:356-362.
    [3] Jiirgen Janke, Stefan Engeli, Michael Boschmann, Frauke Adams, Jana Bohnke, Friedrich C. Luft, Arya M. Sharma, and Jens Jordan.Retinol-Binding Protein 4 in Human Obesity. Diabetes 2006; 55:2805-2810.
    [4] Timothy E. Graham, Qin Yang, Matthias Bl(?)her, Ann Hammarstedt, Theodore P. Ciaraldi, Robert R. Henry, Christopher J. Wason, B.S., Andreas Oberbach, Per-Anders Jansson, Ulf Smith, and Barbara B. Kahn. Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects. N Engl J Med 2006;354:2552-2563.
    [5] Dominik G. Haider, Karin Schindler, Gerhard Prager, Arthur Bohdjalian, Anton Luger, Michael Wolzt and Bernhard Ludvik Serum retinol-binding protein 4 is reduced after weight loss in. morbidly obese subjects. J Clin Endocrinol Metab, 92(3):1168-1171.
    [6] Lee DC; Lee JW; Im JA. Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents. Metabolism 2007; 56(3):327-331.
    [7] Gavi S, Stuart LM, Kelly P, Melendez MM, Mynarcik DC, Gelato MC, McNurlan MA. Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes. J Clin Endocrinol Metab 2007;92(6):1886-1890.
    [8] Young Min Cho, Byung-Soo Youn, et al. Plasma Retinol-Binding Protein-4 Concentrations Are Elevated in Human Subjects With Impaired Glucose Tolerance and Type 2 Diabetes. Diabetes Care 2006; 29(11):2457-61.
    [9] Kohzo Takebayashi, Mariko Suetaugu, et al. Retinol-Binding Protein-4 levels and clinical features of type 2 diabetes patients. J Clin Endocrin Metab 2006;92(6):2712-2719.
    [10] Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E, Fritsche A, H(?)ring HU High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care 2007; 30(5):1173-1178.
    [11] Shai Gavi, Louise M. Stuart, Patricia Kelly, Mark M. Melendez, Dennis C. Mynarcik, Marie C. Gelato and Margaret A. McNurlan. Retinol-Binding Protein 4 Is Associated with Insulin Resistance and Body Fat Distribution in Nonobese Subjects without Type 2 Diabetes. Clin Endocrinol. Metab 2006;92(6): 1886-1890
    [12] Prabhakaran Balagopal, Timothy E. Graham, et al. Reduction of Elevated Serum Retinol Binding Protein in Obese Children by Lifestyle Intervention: Association with Subclinical Inflammation. J Clin Endocrin Metab 2006;92(5): 1971-1974
    [13] Eray Yagmur, Ralf Weiskirchen, et al. Insulin Resistance in Liver Cirrhosis Is Not Associated With Circulating Retinol-Binding Protein 4. Diabetes Care 2007;30(5):1168-1172
    [1] KjeldsenL,Johnsen AH, Sengela H et al. Isolation and primary structure of LCN2, a novel protein associated with human neutrophil gelatisase. J Biol Chem 1993; 268(14):10425.
    [2] Flower DR. The lipocalin protein family: structure and function. Biochem J 1996; 318 (Ptl): 1-14
    [3] Fried A, stoesz SP, Buckley P, et al.Neutrophil gelatinase -associated in mormal and neoplastic human tissues. Cell typespecific pattern of expression.Histochem 1999; 31(7): 433-441
    [4] Kjeldsen L, Bainton DF, Sengel0v H, Borregaard N. Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood 1994; 83(3):799-807.
    [5] Bratt T, Ohlson S, Borregaard N. Interactions between neutrophil gelatinase-associated lipocalin and natural lipophilic ligands. Biochim Biophys Acta 1999; 1472(l-2):262.
    [6] Goetz DH, Willie ST, Armen R S, et al. Ligand preference inferred from the structure of neutrophil gelatinase-associated lipocalin. Biochemistry 2000; 39(8):1935-1941.
    [7] MishraJ, Mori K, ma Q etal. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. Jam Soc Nephrol 2004; 15(12):3073.
    [8] Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, TsoAW, Chow WS, Wat NM, Xu JY, HooRL, XU A: Lipocalin 2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 2007; 53:34-41.
    [9] Lin Y, Rajala MW, berger JP, Moleer DE, Barzilai N,Scherer PE:Hyperglycemia-induced production of acute phase reactants in adipose tissue. J Biol Chem 2001; 276:42077-42083.
    [10] Soukas A, Cohen P Socci ND, Friedman JM: Leptin-specific patterns of gene expression in white adipose tissue. Genes Dev 2000; 14:963-980.
    [11] Baudry A, Yang ZZ, and Hemmings BA: PKBalpha is required for adipose differentiation of mouse embryonic fibroblasts. JCell Sci 2006; 119:889-897.
    [12] Kratchmarova I, Kalume DE, Blagoev B, Schere PE, Podtelejnikov AV, Molina H,Bickel PE, Andersen JS,Fernandez MM,Bunkenbog J, Roepstorff P,Kristiansen K, Lodish HF, Mann M, Pandey A: Aproteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes.Mol Cell Proteomics 2002;l:213-222.
    [13] Qing-Wu Yan, Qin Yang, Nimesh Mody, Timothy E. Graham, Chung -Hsin Hsu, Zhao Xu, et al. The Adipokine Iipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes 2007;56:2533-2540.
    [14] Weisberg SP, Mcann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-1808
    [15] Hotamisligil GS: Inflammation and metabolic disorders. Nature 2006;444:860-867.
    [16] Lin Y, Berg AH, Iyengar P, Lam TK, Giacca A, Combs TP, Rajala MW, Du Brownlee M, Hawkins M, Barzilai N, Rhodes CJ, Fantus IG, Brownlee M, Scherer PE: hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 2005;280:4671-4626.
    [17] Yang J ,Goetz D, Li JY , Wang W, Mori K, Setlik D, Du T, Erdjumentbromage H, Tempst P, Strong R, Barasch J: An iron delivery pathway mediated by a lipocalin. Mol Cell 2002;10:1045-1056.
    [18] Fernandez-Real JM, Lopez-Bermejo A, ricart w:Cross-talk between iron metabolism and diabetes. Diabetes 2002;51:2348-2354.
    [19] Rajpathak S, Ma J, Manson J, Willett WC, and Hu FB: Iron intake and the risk of type 2 diabetes in women: a prospective cohort study. Diabetes Care 2006;29:1370-1376.
    [20] Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM: C/EBPalpha induces adipogenesis through PPARgammma: a unified pathway. Genes Dev 2002;16:22-26.
    [21] Devireddy LR, Gazin C, Zhu X, and Green MR: A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 2005;123:1293-1305.
    [22] Haffner SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol 2006;97:3A-11A
    [23] Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 2006;47:cl9-31
    [24] Fujino RS, Tanaka K, Morimatsu M, Tamuta K, Kogo H, Hara T. Spermatogonial Cell-mediated Activation of An lkappaBzeta-independent NF-kappaB Pathway in Sertoli Cells Induces Transcription of the Lipocalin 2 Gene. Mol Endocrinol 2006;4:904-915
    [25] Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferators-activated receptor agonists. Diabetes 2005;54:2460-70.

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